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Original Articles
- Lung and Thoracic cancer
- Unraveling the Impact of Sarcopenia-Induced Lymphopenia on Treatment Response and Prognosis in Patients with Stage III Non–Small Cell Lung Cancer: Insights for Optimizing Chemoradiation and Immune Checkpoint Inhibitor
- Joongyo Lee, Kyung Hwan Kim, Jina Kim, Chang Geol Lee, Jaeho Cho, Hong In Yoon, Yeona Cho
- Cancer Res Treat. 2025;57(2):422-433. Published online October 30, 2024
- DOI: https://doi.org/10.4143/crt.2024.493
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Abstract
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Supplementary Material
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ePub - Purpose
Sarcopenia is a poor prognostic factor in non–small cell lung cancer (NSCLC). However, its prognostic significance in patients with NSCLC receiving immune checkpoint inhibitors (ICIs) and its relationship with lymphopenia remain unclear. We aimed to investigate the prognostic role of sarcopenia and its effect on lymphocyte recovery in patients with stage III NSCLC treated with concurrent chemoradiotherapy (CCRT) followed by ICI.
Materials and Methods
We retrospectively evaluated 151 patients with stage III NSCLC who received definitive CCRT followed by maintenance ICI between January 2016 and June 2022. Sarcopenia was evaluated by measuring the skeletal muscle area at the L3 vertebra level using computed tomography scans. Lymphocyte level changes were assessed based on measurements taken before and during CCRT and at 1, 2, 3, 6, and 12 months post-CCRT completion.
Results
Even after adjusting for baseline absolute lymphocyte count through propensity score-matching, patients with pre-radiotherapy (RT) sarcopenia (n=86) exhibited poor lymphocyte recovery and a significantly high incidence of grade ≥ 3 lymphopenia during CCRT. Pre-RT sarcopenia and grade ≥ 3 lymphopenia during CCRT emerged as prognostic factors for overall survival and progression-free survival, respectively. Concurrent chemotherapy dose adjustments, objective response after CCRT, and discontinuation of maintenance ICI were also analyzed as independent prognostic factors.
Conclusion
Our results demonstrated an association between pre-RT sarcopenia and poor survival, concurrent chemotherapy dose adjustments, and impaired lymphocyte recovery after definitive CCRT. Moreover, CCRT-induced lymphopenia not only contributed to poor prognosis but may have also impaired the therapeutic efficacy of subsequent maintenance ICI, ultimately worsening treatment outcomes.
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- Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
- Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee
- Cancer Res Treat. 2025;57(1):70-82. Published online August 7, 2024
- DOI: https://doi.org/10.4143/crt.2024.046
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Abstract
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- Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy. -
Citations
Citations to this article as recorded by
- Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
Clelia Madeddu, Eleonora Lai, Manuela Neri, Elisabetta Sanna, Giulia Gramignano, Sonia Nemolato, Mario Scartozzi, Sabrina Giglio, Antonio Macciò
International Journal of Molecular Sciences.2025; 26(5): 2232. CrossRef
- Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
- 1,655 View
- 163 Download
- 1 Web of Science
- 1 Crossref
- Sarcoma
- Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response
- Jung Yong Hong, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Sang Kyum Kim, Yurimi Lee, Yoon-La Choi, Minsuk Kwon, Hyo Song Kim, Jeeyun Lee
- Cancer Res Treat. 2023;55(2):671-683. Published online September 27, 2022
- DOI: https://doi.org/10.4143/crt.2022.251
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Abstract
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- Purpose
Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy.
Materials and Methods
We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA.
Results
Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker.
Conclusion
Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies. -
Citations
Citations to this article as recorded by- Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial
Hee Jin Cho, Kum-Hee Yun, Su-Jin Shin, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Hyang Joo Ryu, Joohee Lee, Iksung Cho, Heounjeong Go, Jiwon Ko, Inkyung Jung, Min Kyung Jeon, Sun Young Rha, Hyo Song Kim
Nature Communications.2024;[Epub] CrossRef - The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease
Jonathan Feicht, Ralf-Peter Jansen
RNA Biology.2024; 21(1): 312. CrossRef - Intracranial Relapse in Pediatric Sarcoma
Danielle E. Smith, Tyler Hamby, Kenneth Heym, Ashraf Mohamed, Kelly L. Vallance, Anish Ray
Journal of Pediatric Hematology/Oncology.2023; 45(7): e810. CrossRef
- Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial
- 5,976 View
- 212 Download
- 3 Web of Science
- 3 Crossref
- Gastrointestinal cancer
- Molecular and Immune Profiling of Syngeneic Mouse Models Predict Response to Immune Checkpoint Inhibitors in Gastric Cancer
- Dagyeong Lee, Junyong Choi, Hye Jeong Oh, In-Hye Ham, Sung Hak Lee, Sachiyo Nomura, Sang-Uk Han, Hoon Hur
- Cancer Res Treat. 2023;55(1):167-178. Published online May 20, 2022
- DOI: https://doi.org/10.4143/crt.2022.094
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Abstract
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- Purpose
Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines.
Materials and Methods
We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing.
Results
The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group.
Conclusion
We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy. -
Citations
Citations to this article as recorded by- Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
Dagyeong Lee, In-Hye Ham, Hye Jeong Oh, Dong Min Lee, Jung Hwan Yoon, Sang-Yong Son, Tae-Min Kim, Jae-Young Kim, Sang-Uk Han, Hoon Hur
Journal of Translational Medicine.2024;[Epub] CrossRef - Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report
Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Liudmila V. Spirina, Alexander M. Volkov
Current Issues in Molecular Biology.2023; 45(9): 7642. CrossRef - Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer
Tae Hoon Kim, Dagyeong Lee, Hye Jeong Oh, In-Hye Ham, Dong Min Lee, Yulim Lee, Zhang Zhang, Ding Ke, Hoon Hur
Life Sciences.2023; 335: 122230. CrossRef
- Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
- 8,773 View
- 434 Download
- 5 Web of Science
- 3 Crossref
- Histopathologic and Molecular Biomarkers of PD-1/PD-L1 Inhibitor Treatment Response among Patients with Microsatellite Instability‒High Colon Cancer
- Jaewon Hyung, Eun Jeong Cho, Jihun Kim, Jwa Hoon Kim, Jeong Eun Kim, Yong Sang Hong, Tae Won Kim, Chang Ohk Sung, Sun Young Kim
- Cancer Res Treat. 2022;54(4):1175-1190. Published online January 12, 2022
- DOI: https://doi.org/10.4143/crt.2021.1133
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Abstract
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- Purpose
Recent clinical trials have reported response rates < 50% among patients treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors for microsatellite instability‒high (MSI-H) colorectal cancer (CRC), and factors predicting treatment response have not been fully identified. This study aimed to identify potential biomarkers of PD-1/PD-L1 inhibitor treatment response among patients with MSI-H CRC.
Materials and Methods
MSI-H CRC patients enrolled in three clinical trials of PD-1/PD-L1 blockade at Asan Medical Center (Seoul, Republic of Korea) were screened and classified into two groups according to treatment response. Their histopathologic features and expression of 730 immune-related genes from the NanoString platform were evaluated, and a machine learning–based classification model was built to predict treatment response among MSI-H CRCs patients.
Results
A total of 27 patients (15 responders, 12 non-responders) were included. A high degree of lymphocytic/neutrophilic infiltration and an expansile tumor border were associated with treatment response and prolonged progression-free survival (PFS), while mucinous/signet-ring cell carcinoma was associated with a lack of treatment response and short PFS. Gene expression profiles revealed that the interferon-γ response pathway was enriched in the responder group. Of the top eight differentially expressed immune-related genes, PRAME had the highest fold change in the responder group. Higher expression of PRAME was independently associated with better PFS along with histologic subtypes in the multivariate analysis. The classification model using these genes showed good performance for predicting treatment response.
Conclusion
We identified histologic and immune-related gene expression characteristics associated with treatment response in MSI-H CRC, which may contribute to optimal patient stratification. -
Citations
Citations to this article as recorded by- The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
Yasemin Cakir, Banu Lebe
Applied Immunohistochemistry & Molecular Morphology.2025; 33(2): 117. CrossRef - Exploration of the regulatory mechanism of norcantharidin on sine oculis homeobox homolog 4 in colon cancer using transcriptome sequencing and bioinformatic
Fanqin Zhang, Chao Wu, Jingyuan Zhang, Zhihong Huang, Antony Stalin, Yiyan Zhai, Shuqi Liu, Jiarui Wu
Journal of Traditional Chinese Medical Sciences.2025; 12(2): 259. CrossRef - Biomarkers to predict efficacy of immune checkpoint inhibitors in colorectal cancer patients: a systematic review and meta-analysis
Hang Yu, Qingquan Liu, Keting Wu, Shuang Tang
Clinical and Experimental Medicine.2024;[Epub] CrossRef - An Insight into the Peculiarities of Signet-Ring Cell Carcinoma of the Colon – a Narrative Review
Loredana Farcaș, Diana Voskuil-Galoș
Journal of Medical and Radiation Oncology.2024; 4(7): 1. CrossRef - High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
Hannah Yang, Beodeul Kang, Yeonjung Ha, Sung Hwan Lee, Ilhwan Kim, Hyeyeong Kim, Won Suk Lee, Gwangil Kim, Sanghoon Jung, Sun Young Rha, Vincent E. Gaillard, Jaekyung Cheon, Chan Kim, Hong Jae Chon
JHEP Reports.2023; 5(4): 100672. CrossRef - Identification of ZBTB4 as an immunological biomarker that can inhibit the proliferation and invasion of pancreatic cancer
Zhe Yang, Feiran Chen, Feng Wang, Xiubing Chen, Biaolin Zheng, Xiaomin Liao, Zhejun Deng, Xianxian Ruan, Jing Ning, Qing Li, Haixing Jiang, Shanyu Qin
BMC Cancer.2023;[Epub] CrossRef - PD-L1 Expression in Colorectal Carcinoma: A Comparison of 3 Scoring Methods in a Cohort of Jordanian Patients
Heyam A. Awad, Maher A. Sughayer, Jumana M. Obeid, Yaqoot N. Heilat, Ahmad S. Alhesa, Reda M. Yousef, Nabil M. Hasasna, Shafiq A. Masoud, Tareq Saleh
Applied Immunohistochemistry & Molecular Morphology.2023; 31(6): 379. CrossRef - Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis
Eun‐Jin Go, Hannah Yang, Wooram Park, Seung Joon Lee, Jun‐Hyeok Han, So Jung Kong, Won Suk Lee, Dong Keun Han, Hong Jae Chon, Chan Kim
Small.2023;[Epub] CrossRef - Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment
Norah A. Alturki
Journal of Clinical Medicine.2023; 12(13): 4301. CrossRef - Enhancing head and neck tumor management with artificial intelligence: Integration and perspectives
Nian-Nian Zhong, Han-Qi Wang, Xin-Yue Huang, Zi-Zhan Li, Lei-Ming Cao, Fang-Yi Huo, Bing Liu, Lin-Lin Bu
Seminars in Cancer Biology.2023; 95: 52. CrossRef - Artificial intelligence for prediction of response to cancer immunotherapy
Yuhan Yang, Yunuo Zhao, Xici Liu, Juan Huang
Seminars in Cancer Biology.2022; 87: 137. CrossRef
- The Relationship of PRAME Expression with Clinicopathologic Parameters and Immunologic Markers in Melanomas: In Silico Analysis
- 7,042 View
- 267 Download
- 8 Web of Science
- 11 Crossref
- Gynecologic cancer
- Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers
- Joseph J. Noh, Min Kyu Kim, Min Chul Choi, Jeong-Won Lee, Hyun Park, Sang Geun Jung, Won Duk Joo, Seung Hun Song, Chan Lee
- Cancer Res Treat. 2022;54(4):1200-1208. Published online December 13, 2021
- DOI: https://doi.org/10.4143/crt.2021.828
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
This study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.
Materials and Methods
We conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.
Results
Among 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129–8.144; p=0.028).
Conclusion
The frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type. -
Citations
Citations to this article as recorded by- Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis
Youwen Zhu, Kun Liu, Hong Zhu
Journal of Gynecologic Oncology.2025;[Epub] CrossRef - ATP13A2 as a prognostic biomarker and its correlation with immune infiltration in cervical cancer: A retrospective study
Zhi Zhao, Yijie Peng, Yuanyuan Yang, Shuaiyu Li, Jiang Ling, Zhenyu Zhu, Chenfeng He
Journal of Cellular and Molecular Medicine.2025;[Epub] CrossRef - Complete remission of a high-risk, locally advanced cervical cancer with para-aortic lymph node metastases treated with first-line tislelizumab plus bevacizumab combined with chemotherapy followed by radiotherapy with maintenance therapy: a case report
Juan Lang, Qianqian Liu, Rong Ji, Miao Qiu, Siben Wang, Qingmeng Liu, Dapeng Li, Ping Chen, Zhongkui Xiong
Frontiers in Immunology.2025;[Epub] CrossRef - Frequency of microsatellite instability in gynecologic cancers and the efficacy of immune checkpoint inhibitors treated: real-world data from a single gynecologic center
Wei Kuang, Jing Zeng, Lingling Tong, Qianqi Liu, Huanxin Sun, Min Feng, Dongni Liang, Wei Wang, Cheng Wang
Frontiers in Immunology.2025;[Epub] CrossRef - Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases
Yu Miyama, Tomomi Kato, Masayasu Sato, Akira Yabuno, Kosei Hasegawa, Masanori Yasuda
Diagnostic Pathology.2024;[Epub] CrossRef - Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST
Shanhui Liang, Huijuan Ge, Shuling Zhou, Jie Tang, Yanzi Gu, Xiaohua Wu, Jin Li
Gynecologic Oncology.2024; 187: 64. CrossRef - Immunotherapy in MMR-d/MSI-H recurrent/metastatic endometrial cancer
Renata Pacholczak-Madej, Michele Bartoletti, Lucia Musacchio, Mirosława Püsküllüoglu, Paweł Blecharz, Domenica Lorusso
Expert Review of Anticancer Therapy.2024; 24(8): 717. CrossRef - Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2
Madeleine Charlotte van den Berg, Hege F Berg, Tomasz Stokowy, Erling A Hoivik, Kathrine Woie, Hilde Engerud, Akinyemi I Ojesina, Ingfrid Salvesen Haldorsen, Jone Trovik, Bjørn I Bertelsen, Camilla Krakstad, Mari Kyllesø Halle
International Journal of Gynecological Cancer.2024; 34(7): 993. CrossRef - Cervical cancer: a new era
Giuseppe Caruso, Matthew K Wagar, Heng-Cheng Hsu, Jorge Hoegl, Guido Martin Rey Valzacchi, Andreina Fernandes, Giuseppe Cucinella, Seda Sahin Aker, Aarthi S Jayraj, Jessica Mauro, Rene Pareja, Pedro T Ramirez
International Journal of Gynecological Cancer.2024; 34(12): 1946. CrossRef - Unraveling the Heterogeneity of Deficiency of Mismatch Repair Proteins in Endometrial Cancer: Predictive Biomarkers and Assessment Challenges
Filomena M. Carvalho, Jesus P. Carvalho
Cancers.2024; 16(20): 3452. CrossRef - Long-term benefit of immunotherapy in a patient with squamous lung cancer exhibiting mismatch repair deficient/high microsatellite instability/high tumor mutational burden: A case report and literature review
Na Li, Zixuan Wan, Dongyan Lu, Ruilian Chen, Xiaowei Ye
Frontiers in Immunology.2023;[Epub] CrossRef - Immune escape and resistance to immunotherapy in mismatch repair deficient tumors
Guillaume Mestrallet, Matthew Brown, Cansu Cimen Bozkus, Nina Bhardwaj
Frontiers in Immunology.2023;[Epub] CrossRef - Heterogeneous expression of mismatch repair proteins and interpretation of immunohistochemical results in colorectal cancer and endometrial cancer
Xiangzhao Li, Shifen Zhang, Jiamin Zeng, Sha-sha Song, Xiaoqing Liu, Wei Kang, Minyi Liang, Rui Yang, Hong Li, Li Liang
Pathology - Research and Practice.2023; 248: 154647. CrossRef - Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies
Migang Kim, Chi-Son Chang, Min Chul Choi, Jeong-Won Lee, Hyun Park, Won Duk Joo
Yonsei Medical Journal.2023; 64(10): 587. CrossRef - Successful neoadjuvant chemotherapy plus sintilimab for locally advanced cervical cancer: case series and review of the literature
Linlin Liu, Xianbo Deng, Shuang Guo, Shouhua Yang
Diagnostic Pathology.2023;[Epub] CrossRef - Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies
Hye-Ji Jung, Jong-Ho Park, Jina Oh, Sae-Mi Lee, Il-Yeo Jang, Jung-Yong Hong, Yoo-Young Lee, Hyun Jin Choi
Cancers.2023; 15(24): 5745. CrossRef - Uterine carcinosarcoma with microsatellite instability - does immunotherapy modify the therapeutic scenario? A case report and literature review
Diocesio Alves Pinto Andrade, Eduardo Paulino, Isabela Panzeri Carlotti Buzatto, Danilo Tadao Wada, Warne Pedro Andrade, Andreia Cristina Melo, Angelica Nogueira-Rodrigues
Brazilian Journal of Oncology.2023;[Epub] CrossRef - Immune checkpoint inhibitors in cervical cancer: Current status and research progress
Yunkai Xie, Weimin Kong, Xiaoling Zhao, He Zhang, Dan Luo, Shuning Chen
Frontiers in Oncology.2022;[Epub] CrossRef
- Immunotherapy plus chemotherapy in patients with advanced endometrial cancer: a cost-effectiveness analysis
- 7,493 View
- 301 Download
- 18 Web of Science
- 18 Crossref
- Lung and Thoracic cancer
- Clinical Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer Patients with Liver Metastases: A Network Meta-Analysis of Nine Randomized Controlled Trials
- Qing Yin, Longguo Dai, Ruizhu Sun, Ping Ke, Liya Liu, Bo Jiang
- Cancer Res Treat. 2022;54(3):803-816. Published online October 25, 2021
- DOI: https://doi.org/10.4143/crt.2021.764
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
This network meta-analysis (NMA) was conducted to compare the efficacy of immune checkpoint inhibitors in advanced non–small cell lung cancer (NSCLC) patients with liver metastases.
Materials and Methods
English literature was retrieved from the PubMed, American Society of Clinical Oncology, and European Society for Medical Oncology databases from January 2015 to January 2021. We pooled the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) using an NMA and ranked treatments by the surface under the cumulative ranking curve. Publication bias was evaluated by Begg’s and Egger’s tests. STATA 15.0 was used for the sensitivity analysis, and the remaining statistical analyses were performed using R 4.0.2.
Results
Nine eligible phase III randomized controlled trials were included, including 1,141 patients with liver metastases. Pembrolizumab+chemotherapy ranked highest, followed by atezolizumab+bevacizumab+chemotherapy and nivolumab. However, no significant difference in OS rates was observed across these three treatments (HR, 0.98; 95% confidence interval [CI], 0.43 to 2.22 for pembrolizumab+chemotherapy vs. atezolizumab+bevacizumab+chemotherapy; HR, 0.91; 95% CI, 0.52 to 1.57 for pembrolizumab+chemotherapy vs. nivolumab). Regarding the PFS rate, atezolizumab+bevacizumab+chemotherapy and pembro-lizumab+chemotherapy ranked highest and no significant difference was observed between them (HR, 0.79; 95% CI, 0.36 to 1.70 for atezolizumab+bevacizumab+chemotherapy vs. pembrolizumab+chemotherapy).
Conclusion
Pembrolizumab+chemotherapy, atezolizumab+bevacizumab+chemotherapy, and nivolumab were superior to other treatments in NSCLC patients with liver metastases. These new findings may help clinicians better select therapeutic strategies for NSCLC patients with liver metastases. -
Citations
Citations to this article as recorded by- The Mechanism of Lactic Acid Regulating Platelet-Derived Microparticles to Affect the Biological Characteristics of Human Lung Adenocarcinoma
红艳 刘
Advances in Clinical Medicine.2025; 15(01): 274. CrossRef - Progress of immune checkpoint inhibitors therapy for non-small cell lung cancer with liver metastases
Fan-jie Qu, Yi Zhou, Shuang Wu
British Journal of Cancer.2024; 130(2): 165. CrossRef - Effectiveness and Safety of Immune Checkpoint Inhibitors Alone or in Combination With Chemotherapy in Pulmonary Sarcomatoid Carcinoma
Daisuke Hazama, Kenji Nakahama, Hiroaki Kodama, Akito Miyazaki, Koichi Azuma, Yosuke Kawashima, Yuki Sato, Kentaro Ito, Yoshimasa Shiraishi, Keita Miura, Takayuki Takahama, Satoshi Oizumi, Yoshinobu Namba, Satoshi Ikeda, Hiroshige Yoshioka, Asuka Tsuya, Y
JTO Clinical and Research Reports.2024; 5(1): 100613. CrossRef - Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer
Lingling Zhu, Xianzhe Yu, Xiaojun Tang, Chenggong Hu, Lei Wu, Yanyang Liu, Qinghua Zhou
Chinese Medical Journal.2024; 137(9): 1019. CrossRef - Treatment Options for Patients with Non-Small Cell Lung Cancer and Liver Metastases
Vesna Ćeriman Krstić, Natalija Samardžić, Milija Gajić, Milan Savić, Biljana Šeha, Marina Roksandić Milenković, Dragana Jovanović
Current Issues in Molecular Biology.2024; 46(12): 13443. CrossRef - Assessing the Relationship Between Liver Metastases and the Survival of Patients With Non-Small Cell Lung Cancer After Immune Checkpoint Inhibitors Treatment: A Systematic Review and Meta-Analysis
Huilin Xu, Pingpo Ming, Zhenyu Zhao, Nan Zhao, Dingjie Zhou, Xixian Tang, Dedong Cao
Integrative Cancer Therapies.2023;[Epub] CrossRef - Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
Handai Xia, Wengang Zhang, Yuqing Zhang, Xiaoling Shang, Yanguo Liu, Xiuwen Wang
Frontiers in Oncology.2022;[Epub] CrossRef
- The Mechanism of Lactic Acid Regulating Platelet-Derived Microparticles to Affect the Biological Characteristics of Human Lung Adenocarcinoma
- 8,158 View
- 259 Download
- 7 Web of Science
- 7 Crossref
- Comparison of the Predictive Power of a Combination versus Individual Biomarker Testing in Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors
- Hyojin Kim, Hyun Jung Kwon, Eun Sun Kim, Soohyeon Kwon, Kyoung Jin Suh, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Jin-Haeng Chung
- Cancer Res Treat. 2022;54(2):424-433. Published online July 7, 2021
- DOI: https://doi.org/10.4143/crt.2021.583
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Since tumor mutational burden (TMB) and gene expression profiling (GEP) have complementary effects, they may have improved predictive power when used in combination. Here, we investigated the ability of TMB and GEP to predict the immunotherapy response in patients with non–small cell lung cancer (NSCLC) and assessed if this combination can improve predictive power compared to that when used individually.
Materials and Methods
This retrospective cohort study included 30 patients with NSCLC who received immune checkpoint inhibitors (ICI) therapy at the Seoul National University Bundang Hospital. programmed cell death-ligand-1 (PD-L1) protein expression was assessed using immunohistochemistry, and TMB was measured by targeted deep sequencing. Gene expression was determined using NanoString nCounter analysis for the PanCancer IO360 panel, and enrichment analysis were performed.
Results
Eleven patients (36.7%) showed a durable clinical benefit (DCB), whereas 19 (63.3%) showed no durable benefit (NDB). TMB and enrichment scores (ES) showed significant differences between the DCB and NDB groups (p=0.044 and p=0.017, respectively); however, no significant correlations were observed among TMB, ES, and PD-L1. ES was the best single biomarker for predicting DCB (area under the curve [AUC], 0.794), followed by TMB (AUC, 0.679) and PD-L1 (AUC, 0.622). TMB and ES showed the highest AUC (0.837) among other combinations (AUC [TMB and PD-L1], 0.777; AUC [PD-L1 and ES], 0.763) and was similar to that of all biomarkers used together (0.832).
Conclusion
The combination of TMB and ES may be an effective predictive tool to identify patients with NSCLC patients who would possibly benefit from ICI therapies. -
Citations
Citations to this article as recorded by- Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
Chuanhao Tang, Zaizai Dong, Shi Yan, Bing Liu, Zhiying Wang, Long Cheng, Feng Liu, Hong Sun, Yimeng Du, Lu Pan, Yuhao Zhou, Zhiyuan Jin, Libo Zhao, Nan Wu, Lingqian Chang, Xiaojie Xu
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Experimental and Therapeutic Medicine.2023;[Epub] CrossRef
- Microdroplet-enhanced chip platform for high-throughput immunotherapy marker screening from extracellular vesicle RNAs and membrane proteins
- 8,312 View
- 223 Download
- 12 Web of Science
- 6 Crossref
- Rare Cancer
- Clinical Experience of Male Primary Choriocarcinoma at the Samsung Medical Center
- Young Sok Ji, Se Hoon Park
- Cancer Res Treat. 2021;53(3):874-880. Published online December 7, 2020
- DOI: https://doi.org/10.4143/crt.2020.1066
-
Abstract
PDFPubReaderePub
- Purpose
The objective of this study was to describe and analyze the clinicopathological features of primary choriocarcinoma (PCC) observed in male patients treated at the Samsung Medical Center between 1996 and 2020.
Materials and Methods
We reviewed the clinical records of 14 male patients with PCC retrospectively to assess their demographic, histological, and clinical characteristics at the time of diagnosis as well as identify the treatment outcomes.
Results
The median age of the patients was 33 years. The primary tumor site was the testicles in seven cases (50%), the mediastinum in six cases (43%), and the brain in one case (7%). The most common metastatic site was the lungs (79%), followed by the brain (43%). All patients with PCC received cytotoxic chemotherapy. Twelve patients had records of their response to cytotoxic chemotherapy; of these 12 patients, eight (8/12, 67%) achieved an objective response, and four (4/12, 33%) achieved stable disease response as the best response during chemotherapy.
Conclusion
It is known that most male PCC patients eventually develop resistance to cytotoxic chemotherapy and die. Factors such as poor response to chemotherapy, high disease burden, brain metastasis, and hemoptysis at the time of diagnosis are associated with shorter survival time in male PCC patients. Programmed death-1/programmed death-ligand 1 blockade therapy can be a salvage treatment for chemotherapy-resistant male PCC patients. -
Citations
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- Immunotherapy
- The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients
- Si-Qi Tang, Ling-Long Tang, Yan-Ping Mao, Wen-Fei Li, Lei Chen, Yuan Zhang, Ying Guo, Qing Liu, Ying Sun, Cheng Xu, Jun Ma
- Cancer Res Treat. 2021;53(2):339-354. Published online November 6, 2020
- DOI: https://doi.org/10.4143/crt.2020.790
-
Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear.
Materials and Methods
Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software.
Results
Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031).
Conclusion
This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs. -
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Iris Teruel, Eva Castellà, Sabela Recalde, Gemma Viñas, Anna Petit, Macedonia Trigueros, Eva Martínez-Balibrea, Eudald Felip, Milana Bergamino, Adrià Bernat-Peguera, Beatriz Cirauqui, Vanesa Quiroga, Angelica Ferrando-Díez, Anna Pous, Assumpció López, Lai
International Journal of Molecular Sciences.2024; 25(22): 12241. CrossRef - Real world comparison of immune-related adverse events with nivolumab-relatlimab versus ipilimumab-nivolumab in patients with advanced cutaneous melanoma
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Targeted Oncology.2023; 18(1): 147. CrossRef - Immune checkpoint inhibitor-induced aplastic anaemia: Case series and large-scale pharmacovigilance analysis
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Frontiers in Pharmacology.2023;[Epub] CrossRef - Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non–Small Cell Lung Cancer
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Gaetano Maria Russo, Anna Russo, Fabrizio Urraro, Fabrizio Cioce, Luigi Gallo, Maria Paola Belfiore, Angelo Sangiovanni, Stefania Napolitano, Teresa Troiani, Pasquale Verolino, Antonello Sica, Gabriella Brancaccio, Giulia Briatico, Valerio Nardone, Alfons
Diagnostics.2023; 13(4): 793. CrossRef - Blood cell counts can predict adverse events of immune checkpoint inhibitors: A systematic review and meta-analysis
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Frontiers in Immunology.2023;[Epub] CrossRef - Gastritis as an immunotherapy-related toxicity in the treatment of endometrial cancer: A case report
Nidhi Goel, Monica D. Levine, Laura M. Chambers, Christa I. Nagel
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Journal for ImmunoTherapy of Cancer.2023; 11(3): e006398. CrossRef - Multidisciplinary recommendations for essential baseline functional and laboratory tests to facilitate early diagnosis and management of immune-related adverse events among cancer patients
Berna C. Özdemir, Cristina Espinosa da Silva, Dimitri Arangalage, Pierre Monney, Sabina A. Guler, Uyen Huynh-Do, Guido Stirnimann, Lucia Possamai, Roman Trepp, Robert Hoepner, Anke Salmen, Camille L. Gerard, Petr Hruz, Lisa Christ, Sacha I. Rothschild
Cancer Immunology, Immunotherapy.2023; 72(7): 1991. CrossRef - Immune checkpoint inhibitor-induced cutaneous toxicities: a review of histopathologic and clinical features
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Human Pathology.2023; 140: 144. CrossRef - Immune checkpoint inhibitors: maximizing benefit whilst minimizing toxicity
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Expert Review of Anticancer Therapy.2023; 23(7): 673. CrossRef - Prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitor treatment
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International Journal of Urology.2023; 30(10): 866. CrossRef - Antinuclear antibody (ANA) status predicts immune-related adverse events in liver cancer patients undergoing anti-PD-1 therapy
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Clinical and Experimental Immunology.2023; 212(3): 239. CrossRef - First-Line, Fixed-Duration Nivolumab Plus Ipilimumab Followed by Nivolumab in Clinically Diverse Patient Populations With Unresectable Stage III or IV Melanoma: CheckMate 401
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American Society of Clinical Oncology Educational Book.2023;[Epub] CrossRef - An updated review of gastrointestinal toxicity induced by PD-1 inhibitors: from mechanisms to management
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British Journal of Haematology.2023; 202(6): 1205. CrossRef - Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors
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European Journal of Cancer.2022; 172: 98. CrossRef - Development of Lymphopenia during Therapy with Immune Checkpoint Inhibitors Is Associated with Poor Outcome in Metastatic Cutaneous Melanoma
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Maciej Borówka, Stanisław Łącki-Zynzeling, Michał Nicze, Sylwia Kozak, Jerzy Chudek
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Korean Journal of Radiology.2022; 23(11): 1089. CrossRef - Use of PD-1 inhibitors in patients with end-stage renal disease: safety and clinical outcomes from real-world data
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Acta Oncologica.2022; 61(9): 1157. CrossRef - Association of High Levels of Antidrug Antibodies Against Atezolizumab With Clinical Outcomes and T-Cell Responses in Patients With Hepatocellular Carcinoma
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JAMA Oncology.2022; 8(12): 1825. CrossRef - Germline genetic variation and predicting immune checkpoint inhibitor induced toxicity
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Anti-Cancer Drugs.2022;[Epub] CrossRef - Vascular Normalization to Improve Treatment of COVID-19: Lessons from Treatment of Cancer
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Clinical Cancer Research.2021; 27(10): 2706. CrossRef - Lenvatinib plus pembrolizumab in patients with advanced or recurrent uterine carcinosarcoma
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Gynecologic Oncology Reports.2021; 37: 100840. CrossRef - Blocking antibody-mediated phosphatidylserine enhances cancer immunotherapy
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Journal of Cancer Research and Clinical Oncology.2021; 147(12): 3639. CrossRef - Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC
Jay M. Lee, Anthony W. Kim, Tomasz Marjanski, Pierre-Emmanuel Falcoz, Masahiro Tsuboi, Yi-Long Wu, Shawn W. Sun, Barbara J. Gitlitz
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Frontiers in Medicine.2021;[Epub] CrossRef
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